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- Title
Exposure to Fine Particulate Air Pollution Causes Vascular Insulin Resistance by Inducing Pulmonary Oxidative Stress.
- Authors
Haberzettl, Petra; O'Toole, Timothy E.; Bhatnagar, Aruni; Conklin, Daniel J.
- Abstract
BACKGROUND: Epidemiological evidence suggests that exposure to ambient air fine particulate matter (PM2.5) increases the risk of developing type 2 diabetes and cardiovascular disease. However, the mechanisms underlying these effects of PM2.5 remain unclear. OBJECTIVES: We tested the hypothesis that PM2.5 exposure decreases vascular insulin sensitivity by inducing pulmonary oxidative stress. METHODS: Mice fed control (10-13% kcal fat) and high-fat (60% kcal fat, HFD) diets, treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPOL) or mice overexpressing lung-specific extracellular superoxide dismutase (ecSOD) were exposed to HEPA-filtered air or to concentrated PM2.5 (CAP) for 9 or 30 days, and changes in systemic and organ-specific insulin sensitivity and inflammation were measured. RESULTS: In control diet -- fed mice, exposure to CAP for 30 days decreased insulin-stimulated Akt phosphorylation in lung, heart, and aorta but not in skeletal muscle, adipose tissue, and liver and did not affect adiposity or systemic glucose tolerance. In HFD-fed mice, 30-day CAP exposure suppressed insulin-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation in skeletal muscle and increased adipose tissue inflammation and systemic glucose intolerance. In control diet -- fed mice, a 9-day CAP exposure was sufficient to suppress insulin-stimulated Akt and eNOS phosphorylation and to decrease IkBα (inhibitor of the transcription factor NF-kB levels in the aorta. Treatment with the antioxidant TEMPOL or lung-specific overexpression of ecSOD prevented CAP-induced vascular insulin resistance and inflammation. CONCLUSIONS: Short-term exposure to PM2.5 induces vascular insulin resistance and inflammation triggered by a mechanism involving pulmonary oxidative stress. Suppression of vascular insulin signaling by PM[sub 2.5] may accelerate the progression to systemic insulin resistance, particularly in the context of diet-induced obesity. CITATION: Haberzettl P, O'Toole TE, Bhatnagar A, Conklin DJ. 2016. Exposure to fine particulate air pollution causes vascular insulin resistance by inducing pulmonary oxidative stress. Environ Health Perspect 124:1830-1839; http://dx.doi.org/10.1289/EHP212
- Subjects
OXIDATIVE stress -- Risk factors; PARTICULATE matter; INSULIN resistance; TYPE 2 diabetes risk factors; CARDIOVASCULAR diseases risk factors; AIR filters; ANIMAL experimentation; CHI-squared test; GENE expression; INFLAMMATION; MICE; OXIDOREDUCTASES; PHOSPHORYLATION; PROBABILITY theory; REGRESSION analysis; RESEARCH funding; STATISTICS; SUPEROXIDE dismutase; T-test (Statistics); DATA analysis; ENVIRONMENTAL exposure; OXIDATIVE stress; CONTROL groups; GLUCOSE intolerance; DATA analysis software; DESCRIPTIVE statistics; ONE-way analysis of variance
- Publication
Environmental Health Perspectives, 2016, Vol 124, Issue 12, p1830
- ISSN
0091-6765
- Publication type
Article
- DOI
10.1289/EHP212